Table of Contents Author Guidelines Submit a Manuscript
International Journal of Alzheimer’s Disease
Volume 2015, Article ID 192747, 11 pages
http://dx.doi.org/10.1155/2015/192747
Review Article

Vitamin D and Alzheimer’s Disease: Neurocognition to Therapeutics

1Department of Biochemistry, ICARE Institute of Medical Sciences and Research, Haldia 721645, India
2Department of Biochemistry, Institute of Post Graduate Medical Education and Research, Kolkata 700020, India

Received 31 May 2015; Accepted 16 July 2015

Academic Editor: Francesco Panza

Copyright © 2015 Anindita Banerjee et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. C. Mount and C. Downton, “Alzheimer disease: progress or profit?” Nature Medicine, vol. 12, no. 7, pp. 780–784, 2006. View at Publisher · View at Google Scholar · View at Scopus
  2. C. P. Ferri, M. Prince, C. Brayne et al., “Global prevalence of dementia: a Delphi consensus study,” The Lancet, vol. 366, no. 9503, pp. 2112–2117, 2005. View at Publisher · View at Google Scholar · View at Scopus
  3. T. J. Montine, W. J. Koroshetz, and D. Babcock, “Recommendations of the Alzheimer's disease-related dementias conference,” Neurology, vol. 83, no. 9, pp. 851–860, 2014. View at Publisher · View at Google Scholar · View at Scopus
  4. H. W. Querfurth and F. M. LaFerla, “Alzheimer's disease,” The New England Journal of Medicine, vol. 362, no. 4, pp. 329–344, 2010. View at Publisher · View at Google Scholar · View at Scopus
  5. D. Praticò, “Oxidative stress hypothesis in Alzheimer's disease: a reappraisal,” Trends in Pharmacological Sciences, vol. 29, no. 12, pp. 609–615, 2008. View at Publisher · View at Google Scholar · View at Scopus
  6. L. H. Kuller, T. J. Littlejohns, W. E. Henley et al., “Vitamin D and the risk of dementia and Alzheimer disease,” Neurology, vol. 83, no. 10, pp. 920–928, 2014. View at Publisher · View at Google Scholar · View at Scopus
  7. N. J. Groves, J. J. McGrath, and T. H. J. Burne, “Vitamin D as a neurosteroid affecting the developing and adult brain,” Annual Review of Nutrition, vol. 34, pp. 117–141, 2014. View at Publisher · View at Google Scholar · View at Scopus
  8. C. Annweiler, M. M. Odasso, S. W. Muir, and O. Beauchet, “Vitamin D and brain imaging in the elderly: should we expect some lesions specifically related to hypovitaminosis D?” The Open Neuroimaging Journal, vol. 6, pp. 16–18, 2012. View at Publisher · View at Google Scholar
  9. E. D. Michos and R. F. Gottesman, “Vitamin D for the prevention of stroke incidence and disability: promising but too early for prime time,” European Journal of Neurology, vol. 20, no. 1, pp. 3–4, 2013. View at Publisher · View at Google Scholar · View at Scopus
  10. L. Jianlin, T. D. Gould, P. Yuan et al., “Post mortem interval effects on the phosphorylation of signalling proteins,” Neuropsychopharmacology, vol. 28, pp. 1017–1025, 2003. View at Google Scholar
  11. J. Götz, J. R. Streffer, D. David et al., “Transgenic animal models of Alzheimer's disease and related disorders: histopathology, behavior and therapy,” Molecular Psychiatry, vol. 9, no. 7, pp. 664–683, 2004. View at Google Scholar · View at Scopus
  12. J. Wang, D. W. Dickson, J. Q. Trojanowski, and V. M.-Y. Lee, “The levels of soluble versus insoluble brain aβ distinguish Alzheimer's disease from normal and pathologic aging,” Experimental Neurology, vol. 158, no. 2, pp. 328–337, 1999. View at Publisher · View at Google Scholar · View at Scopus
  13. A. C. LeBlanc, M. Papadopoulos, C. Bélair et al., “Processing of amyloid precursor protein in human primary neuron and astrocyte cultures,” Journal of Neurochemistry, vol. 68, no. 3, pp. 1183–1190, 1997. View at Google Scholar · View at Scopus
  14. S. H. Choi, Y. H. Kim, M. Hebisch et al., “A three-dimensional human neural cell culture model of Alzheimer's disease,” Nature, vol. 515, no. 7526, pp. 274–278, 2014. View at Publisher · View at Google Scholar · View at Scopus
  15. L. Mucke and D. J. Selkoe, “Neurotoxicity of amyloid β-protein: synaptic and network dysfunction,” Cold Spring Harbor Perspectives in Medicine, vol. 2, no. 7, Article ID a006338, 2012. View at Publisher · View at Google Scholar · View at Scopus
  16. M. G. Savelieff, S. Lee, Y. Liu, and M. H. Lim, “Untangling amyloid-β, tau, and metals in Alzheimer's disease,” ACS Chemical Biology, vol. 8, no. 5, pp. 856–865, 2013. View at Publisher · View at Google Scholar · View at Scopus
  17. G. Perry, A. D. Cash, and M. A. Smith, “Alzheimer disease and oxidative stress,” Journal of Biomedicine and Biotechnology, vol. 2, no. 3, pp. 120–123, 2002. View at Publisher · View at Google Scholar · View at Scopus
  18. R. H. Swerdlow and S. M. Khan, “A ‘mitochondrial cascade hypothesis’ for sporadic Alzheimer's disease,” Medical Hypotheses, vol. 63, no. 1, pp. 8–20, 2004. View at Publisher · View at Google Scholar · View at Scopus
  19. E. Karran, M. Mercken, and B. D. Strooper, “The amyloid cascade hypothesis for Alzheimer's disease: an appraisal for the development of therapeutics,” Nature Reviews Drug Discovery, vol. 10, no. 9, pp. 698–712, 2011. View at Publisher · View at Google Scholar · View at Scopus
  20. W. T. Kimberly, W. Xia, T. Rahmati, M. S. Wolfe, and D. J. Selkoe, “The transmembrane aspartates in presenilin 1 and 2 are obligatory for γ-secretase activity and amyloid β-protein generation,” Journal of Biological Chemistry, vol. 275, no. 5, pp. 3173–3178, 2000. View at Publisher · View at Google Scholar · View at Scopus
  21. A. E. Roher, J. D. Lowenson, S. Clarke et al., “β-amyloid-(1-42) is a major component of cerebrovascular amyloid deposits: implications for the pathology of Alzheimer disease,” Proceedings of the National Academy of Sciences of the United States of America, vol. 90, no. 22, pp. 10836–10840, 1993. View at Publisher · View at Google Scholar · View at Scopus
  22. M. Ahmed, J. Davis, D. Aucoin et al., “Structural conversion of neurotoxic amyloid-β1–42 oligomers to fibrils,” Nature Structural and Molecular Biology, vol. 17, no. 5, pp. 561–567, 2010. View at Publisher · View at Google Scholar · View at Scopus
  23. C. Reitz and R. Mayeux, “Alzheimer disease: epidemiology, diagnostic criteria, risk factors and biomarkers,” Biochemical Pharmacology, vol. 88, no. 4, pp. 640–651, 2014. View at Publisher · View at Google Scholar · View at Scopus
  24. D. K. Lahiri and B. Maloney, “The ‘LEARn’ (Latent Early-life Associated Regulation) model integrates environmental risk factors and the developmental basis of Alzheimer's disease, and proposes remedial steps,” Experimental Gerontology, vol. 45, no. 4, pp. 291–296, 2010. View at Publisher · View at Google Scholar · View at Scopus
  25. E. V. McCollum, N. Simmonds, J. E. Becker, and P. G. Shipley, “An experimental demonstration of the existence of a vitamin which promotes calcium deposition,” The Journal of Biological Chemistry, vol. 53, pp. 293–298, 1922. View at Google Scholar
  26. H. F. DeLuca, “Overview of general physiologic features and functions of vitamin D 1–4,” The American Journal of Clinical Nutrition, vol. 80, no. 6, pp. 16895–16965, 2004. View at Google Scholar · View at Scopus
  27. R. Nair and A. Maseeh, “Vitamin D: the sunshine vitamin,” Journal of Pharmacology and Pharmacotherapeutics, vol. 3, no. 2, pp. 118–126, 2012. View at Publisher · View at Google Scholar · View at Scopus
  28. M. F. Holick, J. A. MacLaughlin, M. B. Clark et al., “Photosynthesis of previtamin D3 in human skin and the physiologic consequences,” Science, vol. 210, no. 4466, pp. 203–205, 1980. View at Publisher · View at Google Scholar · View at Scopus
  29. B. Lehmann and M. Meurer, “Vitamin D metabolism,” Dermatologic Therapy, vol. 23, no. 1, pp. 2–12, 2010. View at Publisher · View at Google Scholar · View at Scopus
  30. D. E. Prosser and G. Jones, “Enzymes involved in the activation and inactivation of vitamin D,” Trends in Biochemical Sciences, vol. 29, no. 12, pp. 664–673, 2004. View at Publisher · View at Google Scholar · View at Scopus
  31. M. F. Holick, “Medical progress: vitamin D deficiency,” The New England Journal of Medicine, vol. 357, no. 3, pp. 266–281, 2007. View at Publisher · View at Google Scholar · View at Scopus
  32. B. Lehmann, O. Tiebel, and M. Meurer, “Expression of vitamin D3 25-hydroxylase (CYP27) mRNA after induction by vitamin D3 or UVB radiation in keratinocytes of human skin equivalents: a preliminary study,” Archives of Dermatological Research, vol. 291, no. 9, pp. 507–510, 1999. View at Publisher · View at Google Scholar · View at Scopus
  33. B. Diesel, M. Seifert, J. Radermacher et al., “Towards a complete picture of splice variants of the gene for 25-hydroxyvitamin D31α-hydroxylase in brain and skin cancer,” Journal of Steroid Biochemistry and Molecular Biology, vol. 89-90, no. 1–5, pp. 527–532, 2004. View at Publisher · View at Google Scholar · View at Scopus
  34. B. Diesel, J. Radermacher, M. Bureik et al., “Vitamin D3 metabolism in human glioblastoma multiforme: functionality of CYP27B1 splice variants, metabolism of calcidiol, and effect of calcitriol,” Clinical Cancer Research, vol. 11, no. 15, pp. 5370–5380, 2005. View at Publisher · View at Google Scholar · View at Scopus
  35. M. F. Holick, “Vitamin D and brain health: the need for vitamin D supplementation and sensible sun exposure,” Journal of Internal Medicine, vol. 277, no. 1, pp. 90–93, 2015. View at Publisher · View at Google Scholar · View at Scopus
  36. G. K. Fu, D. Lin, M. Y. H. Zhang et al., “Cloning of human 25-hydroxyvitamin D-1alpha-hydroxylase and mutations causing vitamin D-dependent rickets type 1,” Molecular Endocrinology, vol. 11, no. 13, pp. 1961–1970, 1997. View at Google Scholar · View at Scopus
  37. I. Neveu, P. Naveilhan, C. Menaa, D. Wion, P. Brachet, and M. Garabedian, “Synthesis of 1,25-dihydroxyvitamin D3 by rat brain macrophages in vitro,” Journal of Neuroscience Research, vol. 38, no. 2, pp. 214–220, 1994. View at Publisher · View at Google Scholar · View at Scopus
  38. P. Naveilhan, I. Neveu, C. Baudet, K. Y. Ohyama, P. Brachet, and D. Wion, “Expression of 25(OH) vitamin D3 24-hydroxylase gene in glial cells,” NeuroReport, vol. 5, no. 3, pp. 255–257, 1993. View at Publisher · View at Google Scholar · View at Scopus
  39. D. J. Llewellyn, K. M. Langa, and I. A. Lang, “Serum 25-hydroxyvitamin D concentration and cognitive impairment,” Journal of Geriatric Psychiatry and Neurology, vol. 22, no. 3, pp. 188–195, 2009. View at Publisher · View at Google Scholar · View at Scopus
  40. D. Gezen-Ak, S. Yılmazer, and E. Dursun, “Why vitamin D in Alzheimer's disease? the hypothesis,” Journal of Alzheimer's Disease, vol. 40, no. 2, pp. 257–269, 2014. View at Publisher · View at Google Scholar · View at Scopus
  41. D. W. Eyles, S. Smith, R. Kinobe et al., “Distribution of the vitamin D receptor and 1 alpha-hydroxylase in human brain,” Journal of Chemical Neuroanatomy, vol. 29, pp. 21–30, 2005. View at Google Scholar
  42. C. Annweiler, M. Montero-Odasso, V. Hachinski, S. Seshadri, R. Bartha, and O. Beauchet, “Vitamin D concentration and lateral cerebral ventricle volume in older adults,” Molecular Nutrition and Food Research, vol. 57, no. 2, pp. 267–276, 2013. View at Publisher · View at Google Scholar · View at Scopus
  43. M. T. Mizwicki, D. Menegaz, J. Zhang et al., “Genomic and nongenomic signaling induced by 1α,25(OH)2-vitamin D3 promotes the recovery of amyloid-β phagocytosis by Alzheimer's disease macrophages,” Journal of Alzheimer's Disease, vol. 29, no. 1, pp. 51–62, 2012. View at Publisher · View at Google Scholar · View at Scopus
  44. J. C. Fleet, “Rapid, membrane-initiated actions of 1,25 dihydroxyvitamin D: what are they and what do they mean?” The Journal of Nutrition, vol. 134, no. 12, pp. 3215–3218, 2004. View at Google Scholar · View at Scopus
  45. M. K. Sutherland, M. J. Somerville, L. K. K. Yoong, C. Bergeron, M. R. Haussler, and D. R. Crapper McLachlan, “Reduction of vitamin D hormone receptor mRNA levels in Alzheimer as compared to Huntington hippocampus: correlation with calbindin-28k mRNA levels,” Molecular Brain Research, vol. 13, no. 3, pp. 239–250, 1992. View at Publisher · View at Google Scholar · View at Scopus
  46. T. B. Moore, H. P. Koeffler, J. M. Yamashiro, and R. K. Wada, “Vitamin D3 analogs inhibit growth and induce differentiation in LA-N-5 human neuroblastoma cells,” Clinical and Experimental Metastasis, vol. 14, no. 3, pp. 239–245, 1996. View at Google Scholar · View at Scopus
  47. M. C. Langub, J. P. Herman, H. H. Malluche, and N. J. Koszewski, “Evidence of functional vitamin D receptors in rat hippocampus,” Neuroscience, vol. 104, no. 1, pp. 49–56, 2001. View at Publisher · View at Google Scholar · View at Scopus
  48. D. Baas, K. Prüfer, M. E. Ittel et al., “Rat oligodendrocytes express the vitamin D3 receptor and respond to 1,25-dihydroxyvitamin D3,” Glia, vol. 31, no. 1, pp. 59–68, 2000. View at Publisher · View at Google Scholar · View at Scopus
  49. T. D. Veenstra, K. Prüfer, C. Koenigsberger, S. W. Brimijoin, J. P. Grande, and R. Kumar, “1,25-Dihydroxyvitamin D3 receptors in the central nervous system of the rat embryo,” Brain Research, vol. 804, no. 2, pp. 193–205, 1998. View at Publisher · View at Google Scholar · View at Scopus
  50. E. Bartoccini, F. Marini, E. Damaskopoulou et al., “Nuclear lipid microdomains regulate nuclear vitamin D3 uptake and influence embryonic hippocampal cell differentiation,” Molecular Biology of the Cell, vol. 22, no. 17, pp. 3022–3031, 2011. View at Publisher · View at Google Scholar · View at Scopus
  51. L. Almeras, D. Eyles, P. Benech et al., “Developmental vitamin D deficiency alters brain protein expression in the adult rat: implications for neuropsychiatric disorders,” Proteomics, vol. 7, no. 5, pp. 769–780, 2007. View at Publisher · View at Google Scholar · View at Scopus
  52. C. Carlberg, “The vitamin D3 receptor in the context of the nuclear receptor superfamily: the central role of the retinoid X receptor,” Endocrine, vol. 4, no. 2, pp. 91–105, 1996. View at Google Scholar
  53. V. C. Yu, C. Delsert, B. Andersen et al., “RXRβ: a coregulator that enhances binding of retinoic acid, thyroid hormone, and vitamin D receptors to their cognate response elements,” Cell, vol. 67, no. 6, pp. 1251–1266, 1991. View at Publisher · View at Google Scholar · View at Scopus
  54. S. A. Kliewer, K. Umesono, D. J. Mangelsdorf, and R. M. Evans, “Retinoid X receptor interacts with nuclear receptors in retinoic acid, thyroid hormone and vitamin D3 signalling,” Nature, vol. 355, no. 6359, pp. 446–449, 1992. View at Publisher · View at Google Scholar · View at Scopus
  55. P. N. MacDonald, T. A. Baudino, H. Tokumaru, D. R. Dowd, and C. Zhang, “Vitamin D receptor and nuclear receptor coactivators: crucial interactions in vitamin D-mediated transcription,” Steroids, vol. 66, no. 3-5, pp. 171–176, 2001. View at Publisher · View at Google Scholar · View at Scopus
  56. J. Brown, J. I. Bianco, J. J. McGrath, and D. W. Eyles, “1,25-Dihydroxyvitamin D3 induces nerve growth factor, promotes neurite outgrowth and inhibits mitosis in embryonic rat hippocampal neurons,” Neuroscience Letters, vol. 343, no. 2, pp. 139–143, 2003. View at Publisher · View at Google Scholar · View at Scopus
  57. P. Calissano, C. Matrone, and G. Amadoro, “Nerve growth factor as a paradigm of neurotrophins related to Alzheimer's disease,” Developmental Neurobiology, vol. 70, no. 5, pp. 372–383, 2010. View at Publisher · View at Google Scholar · View at Scopus
  58. T. D. Veenstra, M. Fahnestock, and R. Kumar, “An AP-1 site in the nerve growth factor promoter is essential for 1,25- dihydroxyvitamin D3-mediated nerve growth factor expression in osteoblasts,” Biochemistry, vol. 37, no. 17, pp. 5988–5994, 1998. View at Publisher · View at Google Scholar · View at Scopus
  59. S. N. Baksi and M. J. Hughes, “Chronic vitamin D deficiency in the weanling rat alters catecholamine metabolism in the cortex,” Brain Research, vol. 242, no. 2, pp. 387–390, 1982. View at Publisher · View at Google Scholar · View at Scopus
  60. E. Puchacz, W. E. Stumpf, E. K. Stachowiak, and M. K. Stachowiak, “Vitamin D increases expression of the tyrosine hydroxylase gene in adrenal medullary cells,” Molecular Brain Research, vol. 36, no. 1, pp. 193–196, 1996. View at Publisher · View at Google Scholar · View at Scopus
  61. E. Garcion, N. Wion-Barbot, C. N. Montero-Menei, F. Berger, and D. Wion, “New clues about vitamin D functions in the nervous system,” Trends in Endocrinology & Metabolism, vol. 13, no. 3, pp. 100–105, 2002. View at Publisher · View at Google Scholar · View at Scopus
  62. D. Gezen-Ak, E. Dursun, and S. Yilmazer, “The effects of vitamin D receptor silencing on the expression of LVSCC-A1C and LVSCC-A1D and the release of NGF in cortical neurons,” PLoS ONE, vol. 6, no. 3, Article ID e17553, 2011. View at Publisher · View at Google Scholar · View at Scopus
  63. L. D. Brewer, V. Thibault, K.-C. Chen, M. C. Langub, P. W. Landfield, and N. M. Porter, “Vitamin D hormone confers neuroprotection in parallel with downregulation of L-type calcium channel expression in hippocampal neurons,” The Journal of Neuroscience, vol. 21, no. 1, pp. 98–108, 2001. View at Google Scholar · View at Scopus
  64. E. Dursun, D. Gezen-Ak, and S. Yilmazer, “A novel perspective for Alzheimer's disease: vitamin D receptor suppression by amyloid-β and preventing the amyloid-β induced alterations by vitamin D in cortical neurons,” Journal of Alzheimer's Disease, vol. 23, no. 2, pp. 207–219, 2011. View at Publisher · View at Google Scholar · View at Scopus
  65. D. Gezen-Ak, E. Dursun, and S. Yilmazer, “Vitamin D inquiry in hippocampal neurons: consequences of vitamin D-VDR pathway disruption on calcium channel and the vitamin D requirement,” Neurological Sciences, vol. 34, no. 8, pp. 1453–1458, 2013. View at Publisher · View at Google Scholar · View at Scopus
  66. E. van Etten and C. Mathieu, “Immunoregulation by 1,25-dihydroxyvitamin D3: basic concepts,” The Journal of Steroid Biochemistry and Molecular Biology, vol. 97, no. 1-2, pp. 93–101, 2005. View at Publisher · View at Google Scholar · View at Scopus
  67. D. W. Eyles, F. Feron, X. Cui et al., “Developmental vitamin D deficiency causes abnormal brain development,” Psychoneuroendocrinology, vol. 34, no. 1, pp. S247–S257, 2009. View at Publisher · View at Google Scholar · View at Scopus
  68. J. Moreno, A. V. Krishnan, D. M. Peehl, and D. Feldman, “Mechanisms of vitamin D-mediated growth inhibition in prostate cancer cells: inhibition of the prostaglandin pathway,” Anticancer Research, vol. 26, no. 4A, pp. 2525–2530, 2006. View at Google Scholar · View at Scopus
  69. A. V. Krishnan and D. Feldman, “Molecular pathways mediating the anti-inflammatory effects of calcitriol: implications for prostate cancer chemoprevention and treatment,” Endocrine-Related Cancer, vol. 17, no. 1, pp. R19–R38, 2010. View at Publisher · View at Google Scholar · View at Scopus
  70. A. Masoumi, B. Goldenson, S. Ghirmai et al., “1α,25-dihydroxyvitamin D3 interacts with curcuminoids to stimulate amyloid-β clearance by macrophages of alzheimer's disease patients,” Journal of Alzheimer's Disease, vol. 17, no. 3, pp. 703–717, 2009. View at Publisher · View at Google Scholar · View at Scopus
  71. S. Ito, S. Ohtsuki, Y. Nezu, Y. Koitabashi, S. Murata, and T. Terasaki, “1α,25-Dihydroxyvitamin D3 enhances cerebral clearance of human amyloid-β peptide(1–40) from mouse brain across the blood-brain barrier,” Fluids and Barriers of the CNS, vol. 8, no. 8, p. 20, 2011. View at Publisher · View at Google Scholar · View at Scopus
  72. J. Yu, M. Gattoni-Celli, H. Zhu et al., “Vitamin D3-enriched diet correlates with a decrease of amyloid plaques in the brain of AβPP transgenic mice,” Journal of Alzheimer's Disease, vol. 25, no. 2, pp. 295–307, 2011. View at Publisher · View at Google Scholar · View at Scopus
  73. G. Carlberg, “The concept of multiple vitamin D signaling pathways,” Journal of Investigative Dermatology Symposium Proceedings, vol. 1, no. 1, pp. 10–14, 1996. View at Google Scholar · View at Scopus
  74. J. Yanagisawa, Y. Yanagi, Y. Masuhiro et al., “Convergence of transforming growth factor-β and vitamin D signaling pathways on SMAD transcriptional coactivators,” Science, vol. 283, no. 5406, pp. 1317–1321, 1999. View at Publisher · View at Google Scholar · View at Scopus
  75. H. Taniura, M. Ito, N. Sanada et al., “Chronic vitamin D3 treatment protects against neurotoxicity by glutamate in association with upregulation of vitamin D receptor mRNA expression in cultured rat cortical neurons,” Journal of Neuroscience Research, vol. 83, no. 7, pp. 1179–1189, 2006. View at Publisher · View at Google Scholar · View at Scopus
  76. M. Ibi, H. Sawada, M. Nakanishi et al., “Protective effects of 1α,25-(OH)2D3 against the neurotoxicity of glutamate and reactive oxygen species in mesencephalic culture,” Neuropharmacology, vol. 40, no. 6, pp. 761–771, 2001. View at Publisher · View at Google Scholar · View at Scopus
  77. V. L. Dawson and T. M. Dawson, “Nitric oxide neurotoxicity,” Journal of Chemical Neuroanatomy, vol. 10, no. 3-4, pp. 179–190, 1996. View at Publisher · View at Google Scholar · View at Scopus
  78. E. Garcion, S. Nataf, A. Berod, F. Darcy, and P. Brachet, “1,25-Dihydroxyvitamin D3 inhibits the expression of inducible nitric oxide synthase in rat central nervous system during experimental allergic encephalomyelitis,” Molecular Brain Research, vol. 45, no. 2, pp. 255–267, 1997. View at Publisher · View at Google Scholar · View at Scopus
  79. E. Garcion, L. Sindji, G. Leblondel, P. Brachet, and F. Darcy, “1,25-dihydroxyvitamin D3 regulates the synthesis of γ-glutamyl transpeptidase and glutathione levels in rat primary astrocytes,” Journal of Neurochemistry, vol. 73, no. 2, pp. 859–866, 1999. View at Publisher · View at Google Scholar · View at Scopus
  80. S. Won, I. Sayeed, B. L. Peterson et al., “Vitamin D prevents hypoxia/reoxygenation-induced blood-brain barrier disruption via Vitamin D receptor-mediated NF-kB signaling pathways,” PLOS ONE, vol. 10, no. 3, Article ID e0122821, 2015. View at Publisher · View at Google Scholar
  81. T. L. Briones and H. Darwish, “Decrease in age-related tau hyperphosphorylation and cognitive improvement following vitamin D supplementation are associated with modulation of brain energy metabolism and redox state,” Neuroscience, vol. 262, pp. 143–155, 2014. View at Publisher · View at Google Scholar · View at Scopus
  82. D. Eyles, L. Almeras, P. Benech et al., “Developmental vitamin D deficiency alters the expression of genes encoding mitochondrial, cytoskeletal and synaptic proteins in the adult rat brain,” Journal of Steroid Biochemistry & Molecular Biology, vol. 103, no. 3–5, pp. 538–545, 2007. View at Publisher · View at Google Scholar · View at Scopus
  83. D. W. Eyles, T. H. J. Burne, and J. J. McGrath, “Vitamin D, effects on brain development, adult brain function and the links between low levels of vitamin D and neuropsychiatric disease,” Frontiers in Neuroendocrinology, vol. 34, no. 1, pp. 47–64, 2013. View at Publisher · View at Google Scholar · View at Scopus
  84. M. Moon, H. Song, H. J. Hong et al., “Vitamin D-binding protein interacts with Aβ and suppresses Aβ-mediated pathology,” Cell Death & Differentiation, vol. 20, no. 4, pp. 630–638, 2013. View at Publisher · View at Google Scholar · View at Scopus
  85. T. J. Wang, M. J. Pencina, S. L. Booth et al., “Vitamin D deficiency and risk of cardiovascular disease,” Circulation, vol. 117, no. 4, pp. 503–511, 2008. View at Publisher · View at Google Scholar · View at Scopus
  86. D. J. Llewellyn, I. A. Lang, K. M. Langa et al., “Vitamin D and risk of cognitive decline in elderly persons,” Archives of Internal Medicine, vol. 170, no. 13, pp. 1135–1141, 2010. View at Publisher · View at Google Scholar · View at Scopus
  87. C. Annweiler and O. Beauchet, “Vitamin D-Mentia: randomized clinical trials should be the next step,” Neuroepidemiology, vol. 37, no. 3-4, pp. 249–258, 2011. View at Publisher · View at Google Scholar · View at Scopus
  88. Y. Slinin, M. L. Paudel, B. C. Taylor et al., “25-Hydroxyvitamin D levels and cognitive performance and decline in elderly men,” Neurology, vol. 74, no. 1, pp. 33–41, 2010. View at Publisher · View at Google Scholar · View at Scopus
  89. T. Etgen, D. Sander, H. Bickel, K. Sander, and H. Förstl, “Vitamin D deficiency, cognitive impairment and dementia: a systematic review and meta-analysis,” Dementia and Geriatric Cognitive Disorders, vol. 33, no. 5, pp. 297–305, 2012. View at Publisher · View at Google Scholar · View at Scopus
  90. C. Balion, L. E. Griffith, L. Strifler et al., “Vitamin D, cognition, and dementia: a systematic review and meta-analysis,” Neurology, vol. 79, no. 13, pp. 1397–1405, 2012. View at Publisher · View at Google Scholar · View at Scopus
  91. J. H. Moon, S. Lim, J. W. Han et al., “Serum 25-hydroxyvitamin D level and the risk of mild cognitive impairment and dementia: the Korean Longitudinal Study on Health and Aging (KLoSHA),” Clinical Endocrinology, vol. 83, no. 1, pp. 36–42, 2015. View at Publisher · View at Google Scholar
  92. Y. Slinin, M. L. Paudel, B. C. Taylor et al., “25-hydroxyvitamin D levels and cognitive performance and decline in elderly men,” Neurology, vol. 74, no. 1, pp. 33–41, 2010. View at Publisher · View at Google Scholar · View at Scopus
  93. C. Annweiler, M. Montero-Odasso, D. J. Llewellyn, S. Richard-Devantoy, G. Duque, and O. Beauchet, “Meta-analysis of memory and executive dysfunctions in relation to vitamin D,” Journal of Alzheimer's Disease, vol. 37, no. 1, pp. 147–171, 2013. View at Publisher · View at Google Scholar · View at Scopus
  94. C. Annweiler, Y. Rolland, A. M. Schott et al., “Higher vitamin D dietary intake is associated with lower risk of Alzheimer's disease: a 7-year follow-up,” The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, vol. 67, no. 11, pp. 1205–1211, 2012. View at Publisher · View at Google Scholar · View at Scopus
  95. C. Anneweiler, E. Dursun, F. Feron et al., “‘Vitamin D and cognition in older adults’: updated international recommendations,” Journal of Internal Medicine, vol. 277, no. 1, pp. 45–57, 2015. View at Google Scholar
  96. A. Serretti, P. Olgiati, and D. De Ronchi, “Genetics of Alzheimer's disease. A rapidly evolving field,” Journal of Alzheimer's Disease, vol. 12, no. 1, pp. 73–92, 2007. View at Google Scholar · View at Scopus
  97. D. Gezen-Ak, E. Dursun, B. Bilgiç et al., “Vitamin D receptor gene haplotype is associated with late-onset Alzheimer's disease,” The Tohoku Journal of Experimental Medicine, vol. 228, no. 3, pp. 189–196, 2012. View at Publisher · View at Google Scholar · View at Scopus
  98. E. Dursun, D. Gezen-Ak, and S. Yilmazer, “Beta amyloid suppresses the expression of the vitamin d receptor gene and induces the expression of the vitamin D catabolic enzyme gene in hippocampal neurons,” Dementia and Geriatric Cognitive Disorders, vol. 36, no. 1-2, pp. 76–86, 2013. View at Publisher · View at Google Scholar · View at Scopus
  99. E. Dursun, D. Gezen-Ak, and S. Yilmazer, “A new mechanism for amyloid-β induction of iNOS: vitamin D-VDR pathway disruption,” Journal of Alzheimer's Disease, vol. 36, no. 3, pp. 459–474, 2013. View at Publisher · View at Google Scholar · View at Scopus
  100. D. Gezen-Ak, E. Dursun, T. Ertan et al., “Association between vitamin D receptor gene polymorphism and Alzheimer's disease,” The Tohoku Journal of Experimental Medicine, vol. 212, no. 3, pp. 275–282, 2007. View at Publisher · View at Google Scholar · View at Scopus
  101. M. A. Beydoun, E. L. Ding, H. A. Beydoun, T. Tanaka, L. Ferrucci, and A. B. Zonderman, “Vitamin D receptor and megalin gene polymorphisms and their associations with longitudinal cognitive change in US adults,” The American Journal of Clinical Nutrition, vol. 95, no. 1, pp. 163–178, 2012. View at Publisher · View at Google Scholar · View at Scopus
  102. T. Keisala, A. Minasyan, Y.-R. Lou et al., “Premature aging in vitamin D receptor mutant mice,” Journal of Steroid Biochemistry and Molecular Biology, vol. 115, no. 3–5, pp. 91–97, 2009. View at Publisher · View at Google Scholar · View at Scopus
  103. A. Minasyan, T. Keisala, Y.-R. Lou, A. V. Kalueff, and P. Tuohimaa, “Neophobia, sensory and cognitive functions, and hedonic responses in vitamin D receptor mutant mice,” Journal of Steroid Biochemistry and Molecular Biology, vol. 104, no. 3–5, pp. 274–280, 2007. View at Publisher · View at Google Scholar · View at Scopus
  104. T. H. J. Burne, A. N. B. Johnston, J. J. McGrath, and A. MacKay-Sim, “Swimming behaviour and post-swimming activity in Vitamin D receptor knockout mice,” Brain Research Bulletin, vol. 69, no. 1, pp. 74–78, 2006. View at Publisher · View at Google Scholar · View at Scopus
  105. J. M. Valdivielso and E. Fernandez, “Vitamin D receptor polymorphisms and diseases,” Clinica Chimica Acta, vol. 371, no. 1-2, pp. 1–12, 2006. View at Publisher · View at Google Scholar · View at Scopus
  106. W.-Z. Ye, A. F. Reis, and G. Velho, “Identification of a novel Tru9 I polymorphism in the human vitamin D receptor gene,” Journal of Human Genetics, vol. 45, no. 1, pp. 56–57, 2000. View at Publisher · View at Google Scholar · View at Scopus
  107. N. A. Morrison, J. C. Qi, A. Tokita et al., “Prediction of bone-density from vitamin D receptor alleles,” Nature, vol. 367, no. 6460, pp. 284–287, 1994. View at Publisher · View at Google Scholar · View at Scopus
  108. N. A. Morrison, R. Yeoman, P. J. Kelly, and J. A. Eisman, “Contribution of trans-acting factor alleles to normal physiological variability: vitamin D receptor gene polymorphisms and circulating osteocalcin,” Proceedings of the National Academy of Sciences of the United States of America, vol. 89, no. 15, pp. 6665–6669, 1992. View at Publisher · View at Google Scholar · View at Scopus
  109. J. H. Faraco, N. A. Morrison, A. Baker, J. Shine, and P. M. Frossard, “ApaI dimorphism at the human vitamin-D receptor gene locus,” Nucleic Acids Research, vol. 17, no. 5, p. 2150, 1989. View at Publisher · View at Google Scholar · View at Scopus
  110. H. Arai, K.-I. Miyamoto, M. Yoshida et al., “The polymorphism in the caudal-related homeodomain protein Cdx-2 binding element in the human vitamin D receptor gene,” Journal of Bone and Mineral Research, vol. 16, no. 7, pp. 1256–1264, 2001. View at Publisher · View at Google Scholar · View at Scopus
  111. D. J. Lehmann, H. Refsum, D. R. Warden, C. Medway, G. K. Wilcock, and A. D. Smith, “The vitamin D receptor gene is associated with Alzheimer's disease,” Neuroscience Letters, vol. 504, no. 2, pp. 79–82, 2011. View at Publisher · View at Google Scholar · View at Scopus
  112. Y. H. Lee, J.-H. Kim, and G. G. Song, “Vitamin D receptor polymorphisms and susceptibility to Parkinson’s disease and Alzheimer’s disease: a meta-analysis,” Neurological Sciences, vol. 35, no. 12, pp. 1947–1953, 2014. View at Publisher · View at Google Scholar · View at Scopus
  113. L. Wang, K. Hara, J. M. Van Baaren et al., “Vitamin D receptor and Alzheimer's disease: a genetic and functional study,” Neurobiology of Aging, vol. 33, no. 8, pp. 1844.e1–1844.e9, 2012. View at Publisher · View at Google Scholar · View at Scopus
  114. R. Anand, K. D. Gill, and A. A. Mahdi, “Therapeutics of Alzheimer's disease: past, present and future,” Neuropharmacology, vol. 76, pp. 27–50, 2014. View at Publisher · View at Google Scholar · View at Scopus
  115. Y. Hong-Qi, S. Zhi-Kun, and C. Sheng-Di, “Current advances in the treatment of Alzheimer's disease: focused on considerations targeting Aβ and tau,” Translational Neurodegeneration, vol. 1, article 21, 2012. View at Publisher · View at Google Scholar · View at Scopus
  116. T. Jiang, J. T. Yu, and L. Tan, “Novel disease modifying therapies for Alzheimer's disease,” Journal of Alzheimer's Disease, vol. 31, no. 3, Article ID 47592, 2012. View at Google Scholar
  117. M. B. H. Youdim and J. J. Buccafusco, “CNS Targets for multi-functional drugs in the treatment of Alzheimer's and Parkinson's diseases,” Journal of Neural Transmission, vol. 112, no. 4, pp. 519–537, 2005. View at Publisher · View at Google Scholar · View at Scopus
  118. C. Annweiler, B. Fantino, E. Parot-Schinkel, S. Thiery, J. Gautier, and O. Beauchet, “Alzheimer's disease—input of vitamin D with memantine assay (AD-IDEA trial): study protocol for a randomized controlled trial,” Trials, vol. 12, article 230, 2011. View at Publisher · View at Google Scholar · View at Scopus
  119. M. Fiala and M. T. Mizwicki, “Neuroprotective and immune effects of active forms of vitamin D3 and docosahexaenoic acid in Alzheimer disease patients,” Functional Foods in Health and Disease, vol. 1, no. 12, pp. 545–554, 2011. View at Google Scholar
  120. C. Annweiler, F. R. Herrmann, B. Fantino, B. Brugg, and O. Beauchet, “Effectiveness of the combination of memantine plus vitamin D on cognition in patients with Alzheimer disease: a pre-post pilot study,” Cognitive & Behavioral Neurology, vol. 25, no. 3, pp. 121–127, 2012. View at Publisher · View at Google Scholar · View at Scopus
  121. M. S. Stein, S. C. Scherer, K. S. Ladd, and L. C. Harrison, “A randomized controlled trial of high-dose vitamin D2 followed by intranasal insulin in Alzheimer's disease,” Journal of Alzheimer's Disease, vol. 26, no. 3, pp. 477–484, 2011. View at Publisher · View at Google Scholar · View at Scopus
  122. R. Przybelski, S. Agrawal, D. Krueger, J. A. Engelke, F. Walbrun, and N. Binkley, “Rapid correction of low vitamin D status in nursing home residents,” Osteoporosis International, vol. 19, no. 11, pp. 1621–1628, 2008. View at Publisher · View at Google Scholar · View at Scopus
  123. K. J. Pepper, S. E. Judd, M. S. Nanes, and V. Tangpricha, “Evaluation of vitamin D repletion regimens to correct vitamin D status in adults,” Endocrine Practice, vol. 15, no. 2, pp. 95–103, 2009. View at Publisher · View at Google Scholar · View at Scopus
  124. M. Schlögl and M. F. Holick, “Vitamin D and neurocognitive function,” Clinical Interventions in Aging, vol. 9, pp. 559–568, 2014. View at Publisher · View at Google Scholar · View at Scopus
  125. R. J. Bishnoi, R. F. Palmer, and D. R. Royall, “Vitamin D binding protein as a serum biomarker of Alzheimer's disease,” Journal of Alzheimer's Disease, vol. 43, no. 1, pp. 37–45, 2015. View at Publisher · View at Google Scholar · View at Scopus